Abstract Purpose Triple-negative breast cancer (TNBC) patients with brain metastases have a poor prognosis and limited treatment options. Preclinical and clinical evidence suggests that radiotherapy may act synergistically with immune checkpoint inhibitors. Methods We conducted an open-label, single-arm, phase II study of atezolizumab plus stereotactic radiosurgery (SRS) in metastatic TNBC patients with brain metastases. The primary endpoint was progression-free survival (PFS) according to the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) bi-compartmental model. Secondary endpoints included extracranial objective response rate, overall survival (OS), and safety and tolerability. A safety run-in analysis for dose-limiting toxicity (DLT) was performed after the first 6 patients were enrolled and completed the assessment period. Results Six patients were enrolled into the safety run-in phase between May 11, 2018 and October 24, 2019. No DLTs were observed, but the study was closed early due to slow accrual. Patients received a median of 2 atezolizumab cycles (range: 2—16), and SRS was administered to all 6 patients. Treatment-related adverse events (TRAEs) occurred in 4 participants (66.7%); all events were grade 2. The median bi-compartmental PFS was 1.3 months (95% confidence interval (CI): 0.95 – NA) and the median OS was 9.7 months (95% CI: 3.6 – NA). The best observed response by RECIST 1.1 criteria was stable disease ≥ 24 weeks in one participant (16.7%). Conclusions Concurrent SRS with atezolizumab was feasible in TNBC patients with brain metastases. However, disease outcomes were poor, and the development of effective therapies for these patients remains a significant unmet medical need. Clinical Trial Registry Number https://www.clinicaltrials.gov NCT03483012. Trial Open to Accrual: 05/01/2018.
Giordano et al. (Sat,) studied this question.